Critical Role of Matrix Metalloproteinase 14 in Adipose Tissue Remodeling during Obesity.
Xin Li,Yueshui Zhao,Chuan Chen,Li Yang,Hyun Ho Lee,Zening Wang,Ningyan Zhang,Mikhail G. Kolonin,Zhiqiang An,Xin Ge,Philipp E. Scherer,Kai Sun +11 more
TLDR
When overexpressing MMP14 in the early-stage obese adipose tissue, the transgenic mice showed a healthier metabolic profile, including ameliorated fibrosis and inflammation, as well as improved lipid and glucose metabolism, which is likely due to digestion/modification of the dense adiposity tissue extracellular matrix by MMP 14, thereby releasing the mechanical stress to allow for its healthy expansion.Abstract:
Fibrosis is recognized as the major pathological change in adipose tissue during the development of obesity. However, the detailed mechanisms governing the interactions between the fibrotic components and their modifiers remain largely unclear. Here, we reported that matrix metalloproteinase 14 (MMP14), a key pericellular collagenase, is dramatically upregulated in obese adipose tissue. We generated a doxycycline-inducible adipose tissue-specific MMP14 overexpression model to study its regulatory function. We found that overexpression of MMP14 in the established obese adipose tissue leads to enlarged adipocytes and increased body weights in transgenic mice. Furthermore, the mice exhibited decreased energy expenditure, impaired lipid metabolism, and insulin resistance. Mechanistically, we found that MMP14 digests collagen 6α3 to produce endotrophin, a potent costimulator of fibrosis and inflammation. Unexpectedly, when overexpressing MMP14 in the early-stage obese adipose tissue, the transgenic mice showed a healthier metabolic profile, including ameliorated fibrosis and inflammation, as well as improved lipid and glucose metabolism. This unique metabolic phenotype is likely due to digestion/modification of the dense adipose tissue extracellular matrix by MMP14, thereby releasing the mechanical stress to allow for its healthy expansion. Understanding these dichotomous impacts of MMP14 provides novel insights into strategies to treat obesity-related metabolic disorders.read more
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Adipose-tissue plasticity in health and disease
TL;DR: Adipose tissue is an extraordinarily flexible and heterogeneous organ as discussed by the authors , and it regulates many aspects of whole-body physiology, including food intake, maintenance of energy levels, insulin sensitivity, body temperature, and immune responses.
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Obesity and diabetes as comorbidities for COVID-19: Underlying mechanisms and the role of viral-bacterial interactions.
TL;DR: It is proposed that interactions of virally-induced ACE2 deficiency with obesity and/or diabetes leads to a synergistic further impairment of endothelial and gut barrier function, resulting in a more severe lung injury in COVID-19.
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Analysis of the intricate effects of polyunsaturated fatty acids and polyphenols on inflammatory pathways in health and disease.
Denisa Margina,Anca Ungurianu,Carmen Purdel,George Mihai Nițulescu,Dimitris Tsoukalas,Evangelia Sarandi,Maria Thanasoula,Tatyana I. Burykina,Fotis Tekos,Aleksandra Buha,Dragana Nikitovic,Demetrios Kouretas,Aristidis Tsatsakis +12 more
TL;DR: In this article, the authors reviewed scientific data from recent publications regarding the beneficial cellular and molecular effects induced by dietary plant products, mainly polyphenolic compounds and PUFAs, and summarize the clinical outcomes expected from these types of interventions, in a search for effective long-term approaches to improve the immune system response.
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Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes.
Tamara Camino,Nerea Lago-Baameiro,Susana B. Bravo,Aurelio M. Sueiro,Iván Couto,Fernando Santos,Javier Baltar,Felipe F. Casanueva,María Pardo +8 more
TL;DR: It is concluded that pathological adipocytes release vesicles containing representative protein cargo of the cell of origin that are able to induce metabolic alterations on healthy cells probably exacerbating the disease once established.
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Adipose Tissue Fibrosis in Obesity: Etiology and Challenges
TL;DR: In this article , the authors highlight adipose tissue remodeling events shown to be associated with fibrosis deposition, with a focus on adipose progenitors involved in obesity-induced healthy as well as unhealthy WAT expansion.
References
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Journal ArticleDOI
How Matrix Metalloproteinases Regulate Cell Behavior
Mark D. Sternlicht,Zena Werb +1 more
TL;DR: Recent advances shed light on how the structure and function of the MMPs are related and on how their transcription, secretion, activation, inhibition, localization, and clearance are controlled.
Journal ArticleDOI
Inflammatory Mechanisms in Obesity
TL;DR: The discovery that obesity itself results in an inflammatory state in metabolic tissues ushered in a research field that examines the inflammatory mechanisms in obesity, and metaflammation is summarized, defined as low-grade, chronic inflammation orchestrated by metabolic cells in response to excess nutrients and energy.
Journal ArticleDOI
Structure and function of matrix metalloproteinases and TIMPs
TL;DR: The members of the MMP family are introduced and their domain structure and function, proenyme activation, the mechanism of inhibition by TIMPs and their significance in physiology and pathology are discussed.
Journal ArticleDOI
Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans
Saverio Cinti,Grant A. Mitchell,Giorgio Barbatelli,Incoronata Murano,Enzo Ceresi,Emanuela Faloia,Shupei Wang,Mélanie Fortier,Andrew S. Greenberg,Martin S. Obin +9 more
TL;DR: It is demonstrated that >90% of all macrophages in WAT of obese mice and humans are localized to dead adipocytes, where they fuse to form syncytia that sequester and scavenge the residual “free” adipocyte lipid droplet and ultimately form multinucleate giant cells, a hallmark of chronic inflammation.
Journal ArticleDOI
What We Talk About When We Talk About Fat
TL;DR: New perspective is gained on the roles played by adipocyte in a variety of homeostatic processes and on the mechanisms used by adipocytes to communicate with other tissues and how these relationships are altered during metabolic disease and how they might be manipulated to restore metabolic health.
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